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目的 探讨环氧化物水解酶 (EPHX)和谷胱甘肽转硫酶 (GST)基因型及血清黄曲霉素B1(AFB1)加成物含量和肝癌易感性的相关性研究。方法 以 3对肝癌高发家族 (6 2例 )和相对应的非癌对照家族成员 (5 8例 )为研究对象 ,分别采用放射免疫法 ,PCR法测定所有成员血清中AFB1 白蛋白加成物量、HBsAg及血细胞的EPHX ,GSTT1,GSTM1的基因型。结果 1.高发家族成员有 4 1.9% (2 6 / 6 2 )血清AFB1 白蛋白加成物含量高于所有被测成员的中位值 ,而对照家族仅有 15 .5 % (9/ 5 8)高于中位值 ,二组之间呈显著性差异 (P <0 .0 0 1)。2 .在对照家族和高发家族AFB1 白蛋白含量低于中位值的人群中GSTM 1,GSTT1,EPHX基因型的分布未见明显的差异 ;而AFB1 白蛋白含量高于中位值的高发家族人群 ,其EPHX 113编码位突变型百分率明显高于对照家族 (P <0 .0 0 1) ,但GSTT1,GSTM 1的基因型的分布无显著性差异。结论 EPHX基因 113编密子的突变与机体AFB1暴露后形成的加成物的含量增加有关 ,从而可以推断与个体对黄曲霉素的敏感性和肝癌的易感性相关。
Objective To investigate the correlation between ephedroic hydrolase (EPHX) and glutathione S-transferase (GST) genotypes and serum aflatoxin B1 (AFB1) adduct content and susceptibility to liver cancer. Methods Three pairs of high incidence of hepatocellular carcinoma (62 cases) and corresponding non-cancer control family members (58 cases) were studied by radioimmunoassay and PCR respectively. The levels of AFB1 albumin adduct, HBsAg and blood cells EPHX, GSTT1, GSTM1 genotype. RESULTS 1. The prevalence of AFB1 albumin adduct was higher in all of the high-risk family members than in all of the tested members (4 1.9% (2 6/62)), compared with 15.5% (9/58) in the control arm ) Was higher than the median, there was a significant difference between the two groups (P <0. 001). There was no significant difference in the distribution of GSTM1, GSTT1 and EPHX genotypes between control and AFB1 albumin levels in patients with high or low prevalence of AFB1 , The percentage of EPHX 113 coding mutation was significantly higher than that of the control family (P <0.01), but the distribution of GSTT1 and GSTM1 genotypes was not significantly different. Conclusion The mutation of codon 113 in EPHX gene is related to the increase of the content of adducts formed after exposure to AFB1 in vivo, which may be related to the individual susceptibility to aflatoxin and the susceptibility to liver cancer.